Ching T L, Haenen G R, Bast A
Faculty of Chemistry, Department of Pharmacochemistry, Vrije Universiteit, Amsterdam, The Netherlands.
Chem Biol Interact. 1993 Feb;86(2):119-27. doi: 10.1016/0009-2797(93)90116-g.
Hydroxyl radical scavengers are able to compete with deoxyribose for the hydroxyl radicals generated in a reaction mixture. We found that the H2 receptor antagonists like cimetidine, burimamide, ranitidine, famotidine and tiotidine except for being good inhibitors in histamine-stimulated gastric acid secretion, were also very powerful hydroxyl radical scavengers. Rate constants for reaction of these drugs with hydroxyl radicals ranged from 7.7 x 10(9) Ms-1 to 14.8 x 10(9) M-1 s-1. These rate constants are much higher than for the well-known hydroxyl radical scavenger mannitol (1.7 x 10(9) M-1 s-1). In this study we investigated which part of the cimetidine molecule might be responsible for its potent hydroxyl radical scavenging activity. Testing fragments of the cimetidine molecule revealed that the guanidine moiety of cimetidine had little hydroxyl radical scavenging activity. However the other part of the molecule, the methylated imidazole with a sulfur and amino group containing side chain appeared to be a powerful hydroxyl radical scavenger.
